The purpose of this component of the Program Project is to use existing and newly developed innovative animal models to investigate the basis of the pathogenesis of Mycobacterium avium infections in the normal and immunodeficient animal. The project will involve experiments designed to monitor the natural course of the infection in such animals, with emphasis on gastrointestinal involvement in order to most closely mimic the apparent course of events in HIV-positive patients. In addition, it will investigate the basis of the host-parasite interaction, including the role of serotype and colony morphotype, in the ability of the organism to persist and/or give rise to infection, and also in terms of the capacity of bacterial cell wall-associated structures to interfere with immune processes. The proposed project is also intimately connected with the other component projects. It will allow a comparison between the biochemical properties of M. avium isolates, their behavior in vivo (Project A); it will provide the means whereby transformed mutants of M. avium can be evaluated in terms of their virulence and infectivity in vivo (Project B); and it will provide the facilities whereby existing and new innovative animal models can be used to evaluate potential new agents in vivo, following their initial identification by in vitro screening and computer predictive modelling (Project D).